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High rate of mobilization for blaCTX-Ms.

Barlow M, Reik RA, Jacobs SD, Medina M, Meyer MP, McGowan JE, Tenover FC - Emerging Infect. Dis. (2008)

Bottom Line: We also found that the blaCTX-Ms are descended from a common ancestor that was incorporated in ancient times into the chromosome of the ancestor of Kluyvera species through horizontal transfer.Considerable sequence divergence has occurred among the descendents of that ancestral gene sequence since that gene was inserted.That divergence has mainly occurred in the presence of purifying selection, which indicates a slow rate of evolution for blaCTX-Ms in the pre-antimicrobial drug era.

View Article: PubMed Central - PubMed

Affiliation: University of California, Merced, California 95344, USA. mbarlow@ucmerced.edu

ABSTRACT
We constructed a phylogenetic analysis of class A beta-lactamases and found that the blaCTX-Ms have been mobilized to plasmids approximately 10 times more frequently than other class A beta-lactamases. We also found that the blaCTX-Ms are descended from a common ancestor that was incorporated in ancient times into the chromosome of the ancestor of Kluyvera species through horizontal transfer. Considerable sequence divergence has occurred among the descendents of that ancestral gene sequence since that gene was inserted. That divergence has mainly occurred in the presence of purifying selection, which indicates a slow rate of evolution for blaCTX-Ms in the pre-antimicrobial drug era.

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Phylogenetic analysis of class A β-lactamases calculated by Bayesian inference. Number of mutations occurring along each branch are represented visually by the lengths of the branches. dN /dS ratios for all branches except the tips are given along the lengths of the branches. Boldface indicates plasmidic genes. Black dots indicate mobilizations to plasmids. Numbered brackets indicate monophyletic divisions within the tree. *dN, nonsynonymous substitution rate; dS, synonoymous substitution rate.
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Figure 2: Phylogenetic analysis of class A β-lactamases calculated by Bayesian inference. Number of mutations occurring along each branch are represented visually by the lengths of the branches. dN /dS ratios for all branches except the tips are given along the lengths of the branches. Boldface indicates plasmidic genes. Black dots indicate mobilizations to plasmids. Numbered brackets indicate monophyletic divisions within the tree. *dN, nonsynonymous substitution rate; dS, synonoymous substitution rate.

Mentions: To compare the number of mobilizations that have occurred in the CTX-M group with those that have occurred in the rest of the class A β-lactamases, we constructed a phylogenetic analysis of class A alleles that spans the breadth of this group and that contains representatives of all groups of class A alleles known to the authors (Figure 2). Among all of the class A β-lactamases, including the blaCTX-Ms, only 22 mobilizations to plasmids were found. To quantitatively compare the numbers of times that CTX-Ms have been mobilized to plasmids with the number of times that other class A β-lactamases have been mobilized to plasmids, the total number of mutations that have occurred within the blaCTX-M clade were summed and divided by the number of mobilizations that have occurred in that region of the phylogenetic analysis. Among the blaCTX-Ms, the ratio of mobilizations to mutations is 1 mobilization per 191 mutations. Among the remainder of the tree when the blaCTX-M clade is excluded from the analysis, 14 mobilizations occur with the ratio of mobilizations to mutations being 1 mobilization per 2,471 mutations. When the complete phylogenetic analysis is considered, 1 mobilization occurs per 1,870 mutations. By that comparison, the mobilization of the blaCTX-M genes to plasmids has occurred at an unusually high rate. This result is unlikely to be an artifact of sampling bias or clinical interest because other class A β-lactamases have been intently studied for a longer period than the blaCTX-Ms. If any bias exists in the data, it would be the undersampling of blaCTX-M mobilizations relative to other class A β-lactamases.


High rate of mobilization for blaCTX-Ms.

Barlow M, Reik RA, Jacobs SD, Medina M, Meyer MP, McGowan JE, Tenover FC - Emerging Infect. Dis. (2008)

Phylogenetic analysis of class A β-lactamases calculated by Bayesian inference. Number of mutations occurring along each branch are represented visually by the lengths of the branches. dN /dS ratios for all branches except the tips are given along the lengths of the branches. Boldface indicates plasmidic genes. Black dots indicate mobilizations to plasmids. Numbered brackets indicate monophyletic divisions within the tree. *dN, nonsynonymous substitution rate; dS, synonoymous substitution rate.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2570810&req=5

Figure 2: Phylogenetic analysis of class A β-lactamases calculated by Bayesian inference. Number of mutations occurring along each branch are represented visually by the lengths of the branches. dN /dS ratios for all branches except the tips are given along the lengths of the branches. Boldface indicates plasmidic genes. Black dots indicate mobilizations to plasmids. Numbered brackets indicate monophyletic divisions within the tree. *dN, nonsynonymous substitution rate; dS, synonoymous substitution rate.
Mentions: To compare the number of mobilizations that have occurred in the CTX-M group with those that have occurred in the rest of the class A β-lactamases, we constructed a phylogenetic analysis of class A alleles that spans the breadth of this group and that contains representatives of all groups of class A alleles known to the authors (Figure 2). Among all of the class A β-lactamases, including the blaCTX-Ms, only 22 mobilizations to plasmids were found. To quantitatively compare the numbers of times that CTX-Ms have been mobilized to plasmids with the number of times that other class A β-lactamases have been mobilized to plasmids, the total number of mutations that have occurred within the blaCTX-M clade were summed and divided by the number of mobilizations that have occurred in that region of the phylogenetic analysis. Among the blaCTX-Ms, the ratio of mobilizations to mutations is 1 mobilization per 191 mutations. Among the remainder of the tree when the blaCTX-M clade is excluded from the analysis, 14 mobilizations occur with the ratio of mobilizations to mutations being 1 mobilization per 2,471 mutations. When the complete phylogenetic analysis is considered, 1 mobilization occurs per 1,870 mutations. By that comparison, the mobilization of the blaCTX-M genes to plasmids has occurred at an unusually high rate. This result is unlikely to be an artifact of sampling bias or clinical interest because other class A β-lactamases have been intently studied for a longer period than the blaCTX-Ms. If any bias exists in the data, it would be the undersampling of blaCTX-M mobilizations relative to other class A β-lactamases.

Bottom Line: We also found that the blaCTX-Ms are descended from a common ancestor that was incorporated in ancient times into the chromosome of the ancestor of Kluyvera species through horizontal transfer.Considerable sequence divergence has occurred among the descendents of that ancestral gene sequence since that gene was inserted.That divergence has mainly occurred in the presence of purifying selection, which indicates a slow rate of evolution for blaCTX-Ms in the pre-antimicrobial drug era.

View Article: PubMed Central - PubMed

Affiliation: University of California, Merced, California 95344, USA. mbarlow@ucmerced.edu

ABSTRACT
We constructed a phylogenetic analysis of class A beta-lactamases and found that the blaCTX-Ms have been mobilized to plasmids approximately 10 times more frequently than other class A beta-lactamases. We also found that the blaCTX-Ms are descended from a common ancestor that was incorporated in ancient times into the chromosome of the ancestor of Kluyvera species through horizontal transfer. Considerable sequence divergence has occurred among the descendents of that ancestral gene sequence since that gene was inserted. That divergence has mainly occurred in the presence of purifying selection, which indicates a slow rate of evolution for blaCTX-Ms in the pre-antimicrobial drug era.

Show MeSH